Dry powder nebulizer

ABSTRACT

A dry powder delivery device may be configured to provide micronized dry powder particles to airways of a user. The device may include a cylindrical container delimiting a chamber containing at least one magnetically-responsive object, a motor external to said chamber, a magnet external to the chamber and rotatably coupled with the motor, and an outflow member configured to direct airflow to a user. The magnetically-responsive object may be coated with micronized dry powder particles, and the motor may be operable to rotate the magnet about an axis. Rotation of the magnet creates a magnetic field that causes the magnetically-responsive object to move in response to the magnetic field and collide with a side wall of the container to deaggregate the dry powder particles and aerosolize the dry powder in the chamber.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/892,900, filed Jun. 4, 2020, which is a continuation of U.S.application Ser. No. 15/676,705, filed Aug. 14, 2017, which is acontinuation of U.S. application Ser. No. 14/739,738, filed Jun. 15,2015, which is a continuation of U.S. application Ser. No. 13/583,606,filed Sep. 7, 2012, which application is a U.S. National Stage Filingunder 35 U.S.C. 371 from International Application No.PCT/US2011/027465, filed on Mar. 8, 2011, and published as WO2011/112531 on Sep. 15, 2011, which claims the benefit of priority ofU.S. provisional application No. 61/311,707, entitled “Dry PowderNebulizer,” filed on Mar. 8, 2010, and U.S. provisional application No.61/456,812, entitled “Dry Powder Nebulizer,” filed on Nov. 12, 2010, thecontents of all of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to systems and methods of deliveringmicronized dry powder particles to the airways of a patient and, moreparticularly, a dry powder nebulizer and method for deliveringmicronized drug powder particles to the deep lung of a patient.

BACKGROUND

Technological advancement in the context of targeted drug delivery tothe lung continues to be an emerging field. The ability to delivertherapeutic agents specifically to the lung has been popular in thetreatment of specific disease states such as asthma, chronic obstructivepulmonary disease (COPD), infections, cancer, and others. Given itsextremely large surface area, mild environment, and ease ofadministration, in contrast to oral and intravenous routes of drugdelivery, the lung presents an especially attractive avenue oftherapeutic delivery.

However, pulmonary drug delivery is not without its obstacles. For drugparticles to deposit in the deep lung, where they exert theirtherapeutic action, they must possess certain physical properties.Specifically, the drug particles must have an aerodynamic diameter below5 microns, where the aerodynamic diameter encompasses both the densityand geometric diameter of the drug particle. Accordingly, aerosolizeddrug particles must be less than 5 microns in aerodynamic diameter whenthey exit an inhaler to deposit in the deep lung.

The majority of devices for targeted drug delivery to the lung can becategorized into one of three groups: metered dose inhalers (MDI), drypowdered inhalers (DPI), and nebulizers. Researchers have advanced eachtechnology to more adequately fit the needs of prescribers, patients,and even environmentalists concerned with the release of ozone-depletingpropellants. While many of the devices currently utilized in theorydeliver a set dose, patient variables such as inspiratory capacity andcoordination alter the performance and thus therapeutic effect achievedthrough the use of the device. Most devices however, deliver only smallquantities of drug per dose or take long periods of time to deliver aclinically relevant dose in many diseases.

Metered-dose inhalers consist of a small device which contains aformulation of drug particles suspended in a liquid. Typically the dosesdelivered by these inhalers are small, in the microgram range, often toosmall for many clinical applications. The patient can then actuate thedevice to receive a set, metered, dose. Although these devices do notrequire a significant inspiratory capacity (30 L/min, e.g.), they dorequire the patient to have been properly counseled and demonstrateconsistent coordination to receive the intended manufacturers' dose.Although spacers and other devices have been developed to circumventthis problem, many patients continue to inappropriately utilize theirdevices, compromising the effectiveness of their medication and leadingto poorer and unpredictable patient outcomes. Formulation problems suchas the inability to include drugs not stable in a liquid environment anda limited shelf-life are also major challenges. Further, propellantswhich used to be included in many formulations to assist in the deliveryprocess, such as chlorofluorocarbons (CFCs), have been suspect in thedepletion of the ozone layer and manufacturers have been required toreformulate their products to contain non-hazardous materials. Thischange has led to patients having to change their products, which arepotentially more expensive and inconsistent in therapeutic efficacy.

Traditional nebulizers are also liquid formulations of drugs which aredelivered to patients who cannot physically actuate or coordinate MDIsor DPIs, primarily young children and the very ill. They carry many ofthe same formulation and stability problems as MDIs and additionally areinefficient, bulky, and require the patient to breathe the contents overlengthy periods of time (15-30 minutes) due to the need to dissolve orfinely disperse the drug within an aqueous liquid. As many medicationsused to treat disease states are prescribed to be taken several times aday, using nebulizers remain an inconvenience to patients and caretakersparticularly due to these long treatment times.

Dry powdered inhalers can be broken down into two subcategories, passiveand active devices. DPIs are formulations of dry powders which areadministered at set doses. Currently, the majority of DPIs on the marketare passive, meaning they are designed to deliver their intended dosewhen the patient has demonstrated a significant inspiratory capacity (60L/min, e.g.) needed to mobilize the powders. Although DPIs are free frommany of the issues and concerns that restrict MDIs and nebulizers (suchas formulation, stability, coordination, and hazardous complications),their performance, and corresponding drug delivery, can be drasticallyimpaired if the patient is unable to inspire at the tested rate; commonin COPD, asthma, and pediatric populations. This, again, can lead tounpredictable and unfavorable patient outcomes if used incorrectly. Forexample, DPI's currently on the market are inadequate because they areliquid formulations, which result in instability, incompatibility, arequirement of advanced coordination, and provide erratic delivery,which in heightened with improper use. Furthermore, the current drypowder formulations have limited delivery and require large inspiratoryforce, adversely affecting the sick, elderly, and children. This hasshown to be problematic for patient populations who have diminished lungfunction resulting from advanced age or the disease process itself.These populations might experience more therapeutic failures and adverseeffects related to the drug due to inability to generate a dispersionpatter reflective of those seen in clinical trials.

In an attempt to mitigate this unpredictability, research groups havefocused on developing active devices. Active devices utilize a powersource to decrease the need for the patient to inspire at the typicalDPI requirement, however, many of these devices have not yet come tomarket and may demonstrate some dosing inconsistencies when used atdifferent patient inspiratory flow rates. In addition, many devices areexceedingly complicated in design and manufacture, adding time and costto the development of therapies. DPIs can deliver a wide range of dosesfrom low micrograms to milligrams. Having the drug in the solid stateenables higher payloads than if the drug needs to be dispersed ordissolved in a solvent. However, as the doses increase, generallyperformance decreases.

Another caveat for targeted drug therapy is payload capabilities. Whenconsidering drug classes such as aminoglycosides and fluoroquinolones,the effectiveness of therapy is dependent on the amount of drug exposedto the site of interest.

It may be desirable to provide a drug delivery device incorporating manyof the beneficial qualities of the above MDI, DPI, and nebulizer devicesas well as additional features which have the potential to benefitseveral disease states, unique from the other devices currently on themarket. It may be desirable to provide consistency in the delivery ofrelatively large doses and intermediate doses under conditions whichmodel inter- and intra-patient variability have historically createdproblems in the performance for standard devices. It may be desirable toprovide a device that offers high doses and excellent performance atvarious flow rates and various orientations (as patients will positionthe device differently each time they use) and aesthetic appeal.Finally, it may be desirable that the device is simple and costminimized.

SUMMARY OF INVENTION

According to various aspects of the disclosure, a dry powder deliverydevice may be configured to provide micronized dry powder particles toairways of a user. The device may include a cylindrical containerdelimiting a chamber containing at least one magnetically-responsiveobject, a motor external to said chamber, a magnet external to thechamber and rotatably coupled with the motor, and an outflow memberconfigured to direct airflow to a user. The magnetically-responsiveobject may be coated with micronized dry powder particles, and the motormay be operable to rotate the magnet about an axis. Rotation of themagnet creates a magnetic field that causes the magnetically-responsiveobject to move in response to the magnetic field and collide with a sidewall of the container to deaggregate the dry powder particles andaerosolize the dry powder in the chamber.

According to some aspects, the magnetically-responsive object maycomprise a magnet such as, for example, a Teflon-coated magnet. In someaspects, the magnetically-responsive object may comprise a capsulecontaining a magnetically-responsive member. The capsule may comprise apolymer.

In accordance with various aspects of the disclosure, a method ofdelivering micronized dry powder particles to a patient may includerotating a magnet exterior to a chamber to create a magnetic field thatcauses responsive movement of at least one magnetically-responsiveobject coated with micronized dry powder particles and contained in thechamber, deaggregates the micronized dry powder particles from themagnetically-responsive object, and aerosolizes the deaggregatedparticles in the chamber. The method further includes directing a flowof air including the aerosolized particles from the chamber to anoutflow member.

In some aspects, the rotating step begins in response to patientactivation, which may include inhalation at a mouthpiece coupled with anoutflow member of the container.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an exemplary dry powder nebulizer inaccordance with various aspects of the disclosure.

FIG. 2 is a perspective view of an exemplary dry powder nebulizer inaccordance with various aspects of the disclosure.

FIG. 3 is a perspective view of an exemplary dry powder nebulizer inaccordance with various aspects of the disclosure.

FIG. 4 is a graph illustrating performance measures of an exemplarynebulizer using ciprofloxacin drug particles.

FIG. 5 is a graph illustrating the quantity (mg) of ciprofloxacindelivered to the “in vitro deep lung” by an exemplary nebulizer.

FIG. 6 is a graph illustrating the percentage of ciprofloxacindistributed in various components of a model airway system and anexemplary nebulizer.

DETAILED DESCRIPTION

FIGS. 1 and 2 illustrate a diagrammatic perspective view of a drugdelivery device comprising an exemplary dry powder nebulizer assembly100 according to various aspects of the disclosure. The dry powdernebulizer assembly 100 includes a container 102 having a top wall 104, abottom wall 106, and at least one side wall 108 extending between thetop and bottom walls 104, 106. The top wall 104, bottom wall 106, andside wall 108 cooperate to delimit a dosing chamber 110. According tovarious aspects, the bottom wall 106 may be pounded out so as to form anuneven, bumpy inner bottom surface of the dosing chamber 110. The effectof the uneven bottom surface is discussed in more detail below.

According to some aspects, the container 102 may comprise a containersuch as, for example, a cylindrical aluminum canister. It should beappreciated that the container may comprise a metal, a polymer, or acombination thereof as long as it is not a paramagnetic material. Insome aspects, a low static material that does not triboelectrify may bedesirable. In some embodiments, the cylindrical canister may measureabout 1.5 to 3 inches in height, for example, about 2.25 inches. In someaspects, the cylindrical canister may taper from the bottom wall 106 totop wall 104. For example, in one exemplary embodiment, the canister maytaper from a diameter of about 0.875 inches at the bottom wall 106 toabout 0.7 inches at the top wall 104. According to various embodiments,the diameter at the bottom wall 106 of the canister may range from 0.7to 1 inch, and the diameter at the top wall 104 of the canister mayrange from about 0.5 to 0.8 inches. It should be appreciated that theseranges are exemplary only and may be lesser or greater depending on theuser's desired parameters.

The container 102 may include one or more air inlets 112 in the sidewall 108. According to some aspects, the container 102 may include twoair inlets 112 provided via hollow shafts 114 disposed at opposite sidesof the container 102 relative to one another. The shafts 114 extendoutward from the container 102 in directions opposite to one another.

The container 102 contains a magnetically responsive object. Referringto FIG. 1 , according to some aspects, the container 102 may contain atleast one miniature magnet 120 in the dosing chamber 110. The at leastone magnet 120 may comprise, for example, a plurality of micron-sized,polymer-coated magnets or magnetically-responsive beads. The number,weight, and size of magnets 120 may vary according to the size of thecontainer 102, the desired dosing, and other design parameters. In someaspects, the magnets 120 may range from about 300 μg to about 1 mg inweight. In some embodiments, the magnets 120 may have a length fromabout 0.35 to 0.4 inches, a width of about 0.1 to 0.15 inches, and athickness of about 0.1 to 0.15 inches. For example, the magnets 120 mayhave a length of about 0.375 inches, a width of about 0.125 inches, anda thickness of about 0.125 inches. It should be appreciated that theaforementioned ranges are exemplary only and may be lesser or greaterdepending on the user's desired parameters. According to some aspects,for example, the magnet(s) or bead(s) may comprise a Teflon-coatedmagnet(s) or bead(s). Further, the polymer-coated magnet(s) or bead(s)includes a desired drug coated thereon.

Referring now to FIG. 2 , in some aspects, a nebulizer assembly mayinclude a container 102 containing at least one capsule 220. In someaspects, the capsule 220 may comprise a polymer or a polymer coating,such as, for example, Teflon. Each capsule 220 contains a pre-measuredamount of drug powder and at least one miniature magnet 222. In someaspects, each magnet 222 may comprise a stir bar or a neodymium magnet,for example. The magnet(s) 222 help to weigh down the capsule(s) 220such that gravity keeps the capsule(s) toward the bottom wall 106 of thecontainer 102 in the dosing chamber 110.

Referring again to FIG. 1 , the nebulizer assembly 100 further includesa motor 150 external to the container 102. The motor 150 may comprise asmall conventional rotational motor, such as for example a motor used intoys and the like. The motor 150 may have a lower power requirement suchthat one or more small button-type batteries, for example three hearingair type batteries, may be employed as a power source and may becontained in a housing associated with the motor. In some embodiments,the motor may operate at approximately 1800 to 2200 revolutions perminute. According to some aspects, the motor 150 may be powered by an acpower source.

The motor 150 may include a magnet 152 coupled with the output shaft 154of the motor 150 so as to rotate therewith. The magnet 152 may comprisea rare earth magnet such as, for example, a neodymium magnet. In someaspects, the magnet 152 may be cylindrical; however, it should beunderstood that other shapes of magnets may be used depending on theuser's desired parameters. It should be appreciate that any other typesof magnets and/or magnetic materials may be utilized. Generally, astronger external magnet 152 may be used if the internal magnets 120,222 are weaker, and a weaker external magnet 152 may be used if theinternal magnets 120, 222 are stronger. The size of the magnet may varybased on the need to create a magnetic field sufficient to influencemovement of the magnets 120 or capsules 220 contained in the dosingchamber 110 of the container 102 when the magnet 152 is placed inproximal relation to an outer surface 140 of the bottom wall 106 of thecontainer 102. According to various aspects, the nebulizer 100 may beactivated when the motor 150 is activated via a patient-operated controlswitch (not shown). In some aspects, the nebulizer 100 may be activatedwhen a patient inhales at the mouthpiece, as would be understood bypersons skilled in the art.

The nebulizer assembly 100 further includes an outflow member 160 fordelivering air containing aerosolized drug particles to a patient. Insome aspects, the outflow member 160 may comprise a conduit, forexample, rubber tubing coupled at one end to the top wall 104 of thecontainer 102 in an airtight relationship. A second, opposite end of theoutflow member 160 may form a mouthpiece 162 configured for insertioninto a patient's mouth during an inhalation procedure. In some aspects,a separate mouthpiece (not shown) may be coupled with the outflow member160. In various aspects, the outflow member 160 and/or mouthpiece may beremovable from the assembly 100 and/or disposable. In some aspects, thetubing may measure approximately 0.8 inches in diameter and 6 incheslength.

The outflow member 160 may contain a filtering member 164 such as, forexample, a mesh for preventing undesired particulate from exiting thenebulizer assembly 100 via the mouthpiece 162 and entering a patient'sairways. According to some embodiments, the filtering member 164 maycomprise non-paramagnetic wiring woven and incorporated in the outflowmember 160 to create a mesh to prevent unwanted particulate fromentering the airways. The container 102 may include an inlet hole 170for dilution air during breathing/inhalation by the patient.

FIG. 3 illustrates a perspective view of an exemplary dry powdernebulizer 300 according to the disclosure. The nebulizer 300 is similarto the exemplary nebulizer 100 described above. However, in thenebulizer 300, the airflow inlets 312 comprise holes 314 in the sidewall 308 of the container 302. FIG. 3 illustrates the holes 314 onopposing regions of the side wall 308 proximate a bottom wall 306 of thecontainer 302. However, it should be appreciated that the holes 314 maybe disposed at other locations along the side wall 308 between thebottom wall 306 and a top wall 304.

In operation, the nebulizer 100, 300 may be activated viapatient-operated switch that activates the motor. Additionally oralternatively, the nebulizer may be activated when a patient inhales atthe mouthpiece, as would be understood by persons skilled in the art.Once the nebulizer 100, 300 is activated, the motor and associatedmagnet turn and generate a magnetic field. The substantially constantrevolution and resulting magnetic field cause the magnets or capsules inthe dosing chamber to continuously collide with the side wall of thedosing chamber. The drug-coated magnet(s) 120 or capsule(s) 220containing drug powder displays a chaotic movement directed by theinfluence of changing magnetic fields induced by the externalmagnet/motor and the internal shape of the dosing/holding chamber thatcauses collisions and forces of deaggregation for the drug-coatedinternal magnet/bead. This force disperses the deaggregated drug into a“cloud” which can then be inhaled by the patient over a set period oftime.

The uneven inner surface of the bottom wall of the container facilitatesthe collisions between the magnets or capsules and the side wall. Theairflow inlets extending tangentially from the side wall of thecontainer proximal the bottom wall help to create an upward cyclonicpush of air during activation of the motor. Such upward cyclonic pushmay improve the aerosolization of the drug powders and reduce the amountof drug which adheres to the inner surface of the side wall of thecontainer, thereby improving efficiency of the nebulizer.

The dosing chamber may include an inlet hole for dilution air duringbreathing/inhalation by the patient. The inhalation aerosol may bedirected from the dosing chamber to the mouthpiece via the outflowmember or other conduit. According to various aspects, the nebulizer mayinclude a mesh, screen, filter, or the like positioned in the path ofairflow from the dosing chamber to the mouthpiece so as to prevent themagnet(s) or bead(s) from leaving the chamber and reaching the patient.

Regarding exemplary embodiments including capsules contained in thedosing chamber of the container, the capsules may contain a premeasuredamount of micronized drug powder encapsulated therein. The capsulesinclude at least one hole sized such that once the nebulizer isactivated, drug can be released via the at least one hole as thecapsules are moved about and collide with the side wall and/or with oneanother in the dosing chamber.

In some aspects, the capsule may be pierced to form one or more holesimmediately prior to use. For example, the ends of the capsule can bepierced with 1-3 pin-sized holes on one or both sides. In some aspects,the capsule may have as few as one hole and as many as six or moreholes, for example. It should be appreciated that the number and size ofthe holes may vary depending on the desired performance of thenebulizer. Persons skilled in the art would understand that theexemplary nebulizers may include a piercer (not shown) associatedtherewith. A user may squeeze a region of the nebulizer to cause thepiercer to pierce the capsule as would be understood by persons skilledin the art.

Regarding exemplary embodiments including a drug-coated micron-sizedmagnet or magnetically-responsive bead, drug powders may be loaded ontothe micron-sized carrier magnets or bead, for example, by affixing asmall spherical canister with loose drug and magnets/beads inside to aslow rotating motor (e.g., as would be seen in a low-tech taperecorder). The magnets/beads are thereby coated with multiple layers ofdrug powder. It should be appreciated that any method of coatingmagnets/beads is contemplated by and consistent with the presentdisclosure.

It should be appreciated that nebulizers consistent with the presentdisclosure may provide customized medication delivery for patients. Itshould also be appreciated that any medication, drug, therapeutic, orother treatment particle desired to be delivered to a patient's airwaysis contemplated by the present disclosure. For example, the amounts (0.5mg to several milligrams) and types of drug powders (antibiotics,long-acting beta agonists, steroids, immunosuppressives, etc.) couldpotentially be varied for patients and compounded based on standardizedmodeling of performance. By doing so, the nebulizer can be tailored to apatient's individual needs. For example, patients might need severalantibiotics for treatment of cystic fibrosis, etc., and nebulizersconsistent with the present disclosure might be able to provide all ofthem to a patient in one treatment. It should be appreciated thattreatments can also be adjusted as the patient's needs change by simplycompounding the capsules/carriers differently.

It should be appreciated that nebulizers consistent with the presentdisclosure may provide one or more advantages such as increasedefficiency, improved stabilization, ease of use, predictable delivery ofmedication, and reproducible delivery. Regarding increased efficiency, asubstantial amount of drug may be delivered over seconds (as compared to15-20 minutes with a traditional nebulizer) without the need of a bulkypower source. Dry powder formulations may provide improved stabilizationbecause such medications are less likely to degrade and dosing can beeasily adjusted for each patient.

It should be appreciated that nebulizers of the present disclosure donot require the coordination needed with conventional metered doseinhalers, nor do they require the inspiratory capacity needed tosufficiently activate a traditional dry powder inhaler. The power sourceused to activate the motor may comprise three conventionally-availablehearing aid batteries, and the overall size of the device may be smallenough to fit in a purse or small carrying device.

It should be appreciated that nebulizers of the present disclosure maydeliver a predictable amount of micronized drug to the “in vitro deeplung” which suggests a patient will receive his/her intended dose in thedesired portion of their airway system. Delivery to the patient may alsobe reproducible despite variations in inspiratory capacity. Tests haveshown that the dispersion of the micronized powders remainssubstantially consistent for airflow rates at 30 L/min and 60 L/min.Therefore, as a patient's lung function changes from day to day(depending on the control of their condition, illness, fatigue, etc.)the same dose can be delivered.

Dispersion studies have been performed using a Next Generation Impactor(NGI), a device designed to model particle deposition in the humanairways. The NGI consists of several components to replicate the mouth,neck, and various sub-fractions of the lung. Tracking how the drugdisperses in the various compartments is necessary to predict theproportion of drug swallowed versus inhaled (a measure to predict sideeffects and systemic absorption through the gastrointestinal tract),drug remaining in the device, and drug which reached the target—the deeplung. Data analysis includes a series of efficiency measures (fineparticle fraction (FPF), respiratory fraction (RF), and the fineparticle dose (FPD)). These parameters are applicable when estimatingthe potential costs associated with the device as well as dosinglimitations and side effects.

The device has shown to be more efficient (relative to other devices onthe market) and consistent in the delivery of our model drug,ciprofloxacin, at a relatively low inspiratory flow rate of 30 L/min forpowder based systems. The majority of the drug that enters the bodyreaches the deep lung, which is a desirable trait when consideringtargeted drug therapy. Further, upon observation, our device seems to berather consistent in delivery despite positioning changes. Our inhaleralso has the ability to deliver large doses of drug over 15-30 secondsat 30 L/min, while maintaining a significantly improved efficiencycompared to those on the market. This may have profound applications ina number of diseases. For example, fungal infections of the lung,especially in neutropenic patients who typically require fungicidalactivity.

Fungal infections of the lung most commonly involve Candida andAspergillus organisms. Many of these organisms have become resistant tothe anti-fungal azole class, and neutropenic patients often requireprolonged hospitalization and intravenous formulations of amphotericin Bor drugs within the echinocandin class, leading to skyrocketinghealthcare costs. In addition to these organisms, other pathogens suchas Cryptococcus continue to surface and pose mortality threats as wellas increased costs. Thus, formulations of amphotericin B and/orcaspofungin (or another from the echinocandin class) complex for use inour device would have significant advantages in therapeutics. This noveland effective method to effectively treat primary fungal infections mayachieve substantially improved patient outcomes (mortality) andcost-effectiveness.

In addition to fungal infections, this technology has the potential totarget other disease states of the lung where large quantities of drugare desired but where the patient lacks the ability to utilize othercurrent methods. Moreover, delivery of high doses of drugs delivered tothe lung for the purposes of systemic absorption is an attractiveapplication and embodiment of the technology.

Example

METHOD: Ciprofloxacin drug particles were jet-milled to micronized drugparticles and loaded onto micron-sized, polymer coated magnets using acustom made tumbling apparatus.

Trials to establish dispersion patterns were conducted using 2drug-loaded magnets. Payload capability data was generated using 4drug-coated magnets.

A custom-made nebulizer device was assembled and comprised a neodyniummagnet fixed upon a handheld, patient-operated, motor-driven rotatingelement external to a chamber where the drug-coated magnets were held.Upon activation of the motor, the rotation of the external magnetcreated a dynamic movement of the drug-coated magnets through magneticfield changes within the chamber (created by the rotating externalmagnet), which led to the production of an aerosolized drug cloud in thecontainer. The outflow conduit of the container was fluidly coupled to amodel airway system so that the aerosolized drug was then able to bedrawn into the model airway system to assess performance.

All studies were conducted using a Next Generation Impactor (NGI®) at 30L/min for 30 seconds. The NGI® is an in vitro model of the human upperairways and lungs designed to predict particle deposition in the humanairways. Concentrations in each component of the device and NGI weredetermined via UV absorbance at 480 nm, from which aerosol distributionpatterns were calculated. Typical efficiency and performance measures,fine-particle fraction (FPF), respirable fraction (RF), andfine-particle dose (FPO), were subsequently calculated.

As used throughout this disclosure, fine-particle fraction refers to theamount (%) of drug delivered to the deep lung (trays 3-8 of the NGI)relative to the amount of drug delivered to the body (mouth, throat,lung (i.e., mouth, ps, and trays 1-8)). The respirable fraction (RF)refers to the amount (%) of drug delivered to the deep lung (trays 3-8of the NGI) relative to the starting dose. The fine particle density(FPO) refers to the amount of drug (micrograms) which penetrate the deeplung (trays 3-8 of the NGI).

RESULTS: Using 2 drug-coated magnets, an average fine-particle fraction(FPF) and respirable fraction (RF) of 75% and 29%, respectively, wasachieved and an average dose of 950 micrograms was delivered to the “invitro deep lung” of the NGI. FIG. 4 illustrates the performance measuresof a device using ciprofloxacin. Fine particle fraction is theproportion of drug that reached the “in vitro deep lung” relative to thetotal amount which entered the NGI. Respirable fraction is theproportion of drug that reached the “in vitro deep lung” relative to thefull dose. That is, respirable fraction accounts for drug which remainedin the nebulizer device and NGI.

When 4 drug-coated magnets were employed, greater than 4.4 milligrams ofciprofloxacin was delivered to the “in vitro deep lung” of the NGI,however the overall efficiency of the set-up was reduced (FPF=48%,RF=17%), as illustrated in FIGS. 4 and 5 . FIG. 6 illustrates thepercentage of ciprofloxacin distributed in various components of themodel airway system (i.e., NGI) and the nebulizer device.

It can be concluded that the low inspiratory capacity needed to generatethe deposition patterns observed may be advantageous when consideringpatient populations who have compromised lung function. The high payloadcapabilities present opportunities to exploit new targeted therapeuticstrategies.

It is noted that, as used in this specification and the appended claims,the singular forms “a,” “an,” and “the” include plural referents unlessotherwise expressly and unequivocally limited to one referent. Thus, forexample, reference to “a nebulizer” includes two or more differentnebulizers. As used herein, the term “include” and its grammaticalvariants are intended to be non-limiting, such that the recitation ofitems in a list is not to the exclusion of other like items that can besubstituted or other items that can be added to the listed items.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the systems and methods ofthe present disclosure without departing from the scope of theinvention. Other embodiments of the invention will be apparent to thoseskilled in the art from consideration of the specification and practiceof the invention disclosed herein. It is intended that the specificationand examples be considered as exemplary only.

What is claimed is:
 1. A dry powder delivery device configured to provide micronized dry powder particles to airways of a user, the device comprising: a cylindrical container delimiting a chamber containing at least one magnetically-responsive object, said object being coated with micronized dry powder particles; a motor external to said chamber; a magnet rotatably coupled with the motor, said motor being operable to rotate the magnet about an axis, said magnet being exterior to said chamber; and an outflow member configured to direct airflow to a user, wherein rotation of the magnet creates a magnetic field that causes said at least one object to move in response to the magnetic field and collide with a side wall of the container to deaggregate the dry powder particles and aerosolize the dry powder in the chamber. 